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1.
Curr Opin Chem Biol ; 56: 98-110, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32446179

RESUMO

G protein-coupled receptors (GPCRs), the largest family of signaling membrane proteins, are the target of more than 30% of the drugs on the market. Recently, it has become clear that GPCR functions are far more multidimensional than previously thought, with multiple noncanonical aspects coming to light, including biased, oligomeric, and compartmentalized signaling. These additional layers of functional selectivity greatly expand opportunities for advanced therapeutic interventions, but the development of new chemical biology tools is absolutely required to improve our understanding of noncanonical GPCR regulation and pave the way for future drugs. In this opinion, we highlight the most notable examples of chemical and chemogenetic tools addressing new paradigms in GPCR signaling, discuss their promises and limitations, and explore future directions.

2.
Br J Nutr ; 123(12): 1321-1332, 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32100651

RESUMO

Mycoprotein is a food high in both dietary fibre and non-animal-derived protein. Global mycoprotein consumption is increasing, although its effect on human health has not yet been systematically reviewed. This study aims to systematically review the effects of mycoprotein on glycaemic control and energy intake in humans. A literature search of randomised controlled trials was performed in PubMed, Embase, Web of Science, Google Scholar and hand search. A total of twenty-one studies were identified of which only five studies, totalling 122 participants, met the inclusion criteria. All five studies were acute studies of which one reported outcomes on glycaemia and insulinaemia, two reported on energy intake and two reported on all of these outcomes. Data were extracted, and risk-of-bias assessment was then conducted. The results did not show a clear effect of acute mycoprotein on blood glucose levels, but it showed a decrease in insulin levels. Acute mycoprotein intake also showed to decrease energy intake at an ad libitum meal and post-24 h in healthy lean, overweight and obese humans. In conclusion, the acute ingestion of mycoprotein reduces energy intake and insulinaemia, whereas its impact on glycaemia is currently unclear. However, evidence comes from a very limited number of heterogeneous studies. Further well-controlled studies are needed to elucidate the short- and long-term effects of mycoprotein intake on glycaemic control and energy intake, as well as the mechanisms underpinning these effects.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32049634

RESUMO

OBJECTIVES: The management of patients with long-standing type 2 diabetes and obesity receiving insulin therapy (IT) is a substantial clinical challenge. Our objective was to examine the effect of a low-energy total diet replacement (TDR) intervention versus standardized dietetic care in patients with long-standing type 2 diabetes and obesity receiving IT. RESEARCH DESIGN AND METHODS: In a prospective randomized controlled trial, 90 participants with type 2 diabetes and obesity receiving IT were assigned to either a low-energy TDR (intervention) or standardized dietetic care (control) in an outpatient setting. The primary outcome was weight loss at 12 months with secondary outcomes including glycemic control, insulin burden and quality of life (QoL). RESULTS: Mean weight loss at 12 months was 9.8 kg (SD 4.9) in the intervention and 5.6 kg (SD 6.1) in the control group (adjusted mean difference -4.3 kg, 95% CI -6.3 to 2.3, p<0.001). IT was discontinued in 39.4% of the intervention group compared with 5.6% of the control group among completers. Insulin requirements fell by 47.3 units (SD 36.4) in the intervention compared with 33.3 units (SD 52.9) in the control (-18.6 units, 95% CI -29.2 to -7.9, p=0.001). Glycated Hemoglobin (HbA1c) fell significantly in the intervention group (4.7 mmol/mol; p=0.02). QoL improved in the intervention group of 11.1 points (SD 21.8) compared with 0.71 points (SD 19.4) in the control (8.6 points, 95% CI 2.0 to 15.2, p=0.01). CONCLUSIONS: Patients with advanced type 2 diabetes and obesity receiving IT achieved greater weight loss using a TDR intervention while also reducing or stopping IT and improving glycemic control and QoL. The TDR approach is a safe treatment option in this challenging patient group but requires maintenance support for long-term success. TRIAL REGISTRATION NUMBER: ISRCTN21335883.

4.
Food Funct ; 11(1): 617-627, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31859318

RESUMO

Refined starchy foods are usually rapidly digested, leading to poor glycaemic control, but not all starchy foods are the same. Complex carbohydrates like resistant starch (RS) have been shown to reduce the metabolic risk factors for chronic diseases such as hyperglycaemia and overweight. The aim of the project was to develop a semolina-based food made from a starch branching enzyme II (sbeIIa/b-AB) durum wheat mutant with a high RS content and to measure its glycaemic index using a double-blind randomised pilot study. We report here the amylose, RS and non-starch polysaccharide concentration of raw sbeIIa/b-AB and wild-type control (WT) semolina. We measured RS after cooking to identify a model food for in vivo testing. Retrograded sbeIIa/b-AB semolina showed a higher RS concentration than the WT control (RS = 4.87 ± 0.6 g per 100 g, 0.77 ± 0.34 g per 100 g starch DWB, respectively), so pudding was selected as the test food. Ten healthy participants consumed ∼50 g of total starch from WT and sbeIIa/b-AB pudding and a standard glucose drink. Capillary blood glucose concentrations were measured in the fasting and postprandial state (2 h): incremental area-under-the-curve (iAUC) and GI were calculated. We found no evidence of difference in GI between sbeIIa/b-AB pudding and the WT control, but the starch digestibility was significantly lower in sbeIIa/b-AB pudding compared to the WT control in vitro (C90 = 33.29% and 47.38%, respectively). Based on these results, novel sbeIIa/b-AB wheat foods will be used in future in vivo studies to test the effect of different RS concentrations and different food matrices on glycaemia.

5.
PLoS One ; 14(11): e0224565, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31725748

RESUMO

BACKGROUND: Muscle wasting in the critically ill is up to 2% per day and delays patient recovery and rehabilitation. It is linked to inflammation, organ failure and severity of illness. The aims of this study were to understand the relationship between muscle depth loss, and nutritional and inflammatory markers during prolonged critical illness. Secondly, to identify when during critical illness catabolism might decrease, such that targeted nutritional strategies may logically be initiated. METHODS: This study was conducted in adult intensive care units in two large teaching hospitals. Patients anticipated to be ventilated for >48 hours were included. Serum C-reactive protein (mg/L), urinary urea (mmol/24h), 3-methylhistidine (µmol/24h) and nitrogen balance (g/24h) were measured on days 1, 3, 7 and 14 of the study. Muscle depth (cm) on ultrasound were measured on the same days over the bicep (bicep and brachialis muscle), forearm (flexor compartment of muscle) and thigh (rectus femoris and vastus intermedius). RESULTS: Seventy-eight critically ill patients were included with mean age of 59 years (SD: 16) and median Intensive care unit (ICU) length of stay of 10 days (IQR: 6-16). Starting muscle depth, 8.5cm (SD: 3.2) to end muscle depth, 6.8cm (SD: 2.2) were on average significantly different over 14 days, with mean difference -1.67cm (95%CI: -2.3 to -1cm), p<0.0001. Protein breakdown and inflammation continued over 14 days of the study. CONCLUSION: Our patients demonstrated a continuous muscle depth loss and negative nitrogen balance over the 14 days of the study. Catabolism remained dominant throughout the study period. No obvious 'nutritional tipping point" to identify anabolism or recovery could be identified in our cohort. Our ICU patient cohort is one with a moderately prolonged stay. This group showed little consistency in data, reflecting the individuality of both disease and response. The data are consistent with a conclusion that a time based assumption of a tipping point does not exist. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN79066838. Registration 25 July 2012.


Assuntos
Proteína C-Reativa/metabolismo , Citidina/análogos & derivados , Tempo de Internação , Músculo Esquelético , Atrofia Muscular , Ureia/urina , Adulto , Idoso , Estado Terminal , Citidina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Atrofia Muscular/sangue , Atrofia Muscular/fisiopatologia , Atrofia Muscular/urina
6.
Am J Epidemiol ; 188(10): 1858-1867, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31318012

RESUMO

The Oxford WebQ is an online 24-hour dietary questionnaire that is appropriate for repeated administration in large-scale prospective studies, including the UK Biobank study and the Million Women Study. We compared the performance of the Oxford WebQ and a traditional interviewer-administered multiple-pass 24-hour dietary recall against biomarkers for protein, potassium, and total sugar intake and total energy expenditure estimated by accelerometry. We recruited 160 participants in London, United Kingdom, between 2014 and 2016 and measured their biomarker levels at 3 nonconsecutive time points. The measurement error model simultaneously compared all 3 methods. Attenuation factors for protein, potassium, total sugar, and total energy intakes estimated as the mean of 2 applications of the Oxford WebQ were 0.37, 0.42, 0.45, and 0.31, respectively, with performance improving incrementally for the mean of more measures. Correlation between the mean value from 2 Oxford WebQs and estimated true intakes, reflecting attenuation when intake is categorized or ranked, was 0.47, 0.39, 0.40, and 0.38, respectively, also improving with repeated administration. These correlations were similar to those of the more administratively burdensome interviewer-based recall. Using objective biomarkers as the standard, the Oxford WebQ performs well across key nutrients in comparison with more administratively burdensome interviewer-based 24-hour recalls. Attenuation improves when the average value is taken over repeated administrations, reducing measurement error bias in assessment of diet-disease associations.


Assuntos
Inquéritos sobre Dietas/métodos , Acelerometria , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Proteínas Sanguíneas/análise , Dióxido de Carbono/metabolismo , Dieta/estatística & dados numéricos , Carboidratos da Dieta/administração & dosagem , Ingestão de Energia , Metabolismo Energético , Feminino , Humanos , Entrevistas como Assunto , Londres , Masculino , Rememoração Mental , Sistemas On-Line , Consumo de Oxigênio , Potássio/sangue , Reprodutibilidade dos Testes , Inquéritos e Questionários
7.
FASEB J ; 33(9): 10280-10290, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31238007

RESUMO

Metabolic challenge tests may be a valuable tool to magnify the effects of diet on health. The use of transcriptomics enables a more extensive characterization of the effects of diet. The question remains whether transcriptome time-course analyses during challenge tests will deliver more information on the effect of diet than a static fasting measurement. A dietary intervention known to improve health is energy restriction (ER). Seventy-two healthy, overweight men and women aged 50-65 were subjected to an oral glucose tolerance test (OGTT) and a mixed-meal test (MMT) before and after 12 wk of a 20% ER diet or control diet. Whole-genome gene expression of peripheral blood mononuclear cells was performed before and after the intervention. This was done during fasting, during the OGTT at 30, 60, and 120 min, and during the MMT at 60, 120, 240, and 360 min. Upon ER, the OGTT resulted in a faster and more pronounced down-regulation in gene expression of oxidative phosphorylation, cell adhesion, and DNA replication compared with the control. The MMT showed less-consistent effects. The OGTT combined with transcriptomics can be used to measure dynamic cellular adaptation upon an intervention that cannot be determined with a static fasting measurement.-Van Bussel, I. P. G., Fazelzadeh, P., Frost, G. S., Rundle, M., Afman, L. A. Measuring phenotypic flexibility by transcriptome time-course analyses during challenge tests before and after energy restriction.

8.
Nutrients ; 11(4)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995824

RESUMO

Supplementation with inulin-propionate ester (IPE), which delivers propionate to the colon, suppresses ad libitum energy intake and stimulates the release of satiety hormones acutely in humans, and prevents weight gain. In order to determine whether IPE remains effective when incorporated into food products (FP), IPE needs to be added to a widely accepted food system. A bread roll and fruit smoothie were produced. Twenty-one healthy overweight and obese humans participated. Participants attended an acclimatisation visit and a control visit where they consumed un-supplemented food products (FP). Participants then consumed supplemented-FP, containing 10 g/d inulin or IPE for six days followed by a post-supplementation visit in a randomised crossover design. On study visits, supplemented-FP were consumed for the seventh time and ad libitum energy intake was assessed 420 min later. Blood samples were collected to assess hormones and metabolites. Resting energy expenditure (REE) was measured using indirect calorimetry. Taste and appearance ratings were similar between FP. Ad libitum energy intake was significantly different between treatments, due to a decreased intake following IPE-FP. These observations were not related to changes in blood hormones and metabolites. There was an increase in REE following IPE-FP. However, this effect was lost after correcting for changes in fat free mass. Our results suggest that IPE suppresses appetite and may alter REE following its incorporation into palatable food products.


Assuntos
Apetite/efeitos dos fármacos , Metabolismo Basal/efeitos dos fármacos , Suplementos Nutricionais , Manipulação de Alimentos , Inulina/farmacologia , Obesidade , Propionatos/farmacologia , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Calorimetria Indireta , Colo , Estudos Cross-Over , Método Duplo-Cego , Ingestão de Energia/efeitos dos fármacos , Feminino , Hormônios/sangue , Humanos , Inulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/metabolismo , Obesidade/fisiopatologia , Sobrepeso , Propionatos/uso terapêutico , Descanso , Resposta de Saciedade/efeitos dos fármacos , Paladar
9.
Gut ; 68(8): 1430-1438, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30971437

RESUMO

OBJECTIVE: To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses. DESIGN: Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period. RESULTS: Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose. CONCLUSION: These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.


Assuntos
Microbioma Gastrointestinal/fisiologia , Insulina/metabolismo , Inulina , Metaboloma/fisiologia , Obesidade , Sobrepeso , Adulto , Índice de Massa Corporal , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Fezes/microbiologia , Feminino , Humanos , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Inulina/administração & dosagem , Inulina/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/dietoterapia , Obesidade/metabolismo , Sobrepeso/diagnóstico , Sobrepeso/dietoterapia , Sobrepeso/metabolismo , Propionatos/administração & dosagem , Propionatos/metabolismo , Resultado do Tratamento
10.
Nutrients ; 10(10)2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30336580

RESUMO

We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial ('RISCK' study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline (n = 469), and on the change in these variables after 24 weeks of dietary intervention (n = 389). At baseline, carriers of E2 (n = 70), E4 (n = 125) and E3/E3 (n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p < 0.0001), apolipoprotein B (apo B, p < 0.0001) and total to high density lipoprotein cholesterol ratio (TC:HDL-C, p = 0.002), with plasma concentrations decreasing in the order E4 > E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC (p = 0.02) and apo B (p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC -0.28 mmol/L p = 0.03; apo B -0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates.


Assuntos
Apolipoproteína E4/genética , Colesterol/sangue , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Ácidos Graxos Monoinsaturados/farmacologia , Comportamento Alimentar , Índice Glicêmico , Adulto , Idoso , Alelos , Apolipoproteína E4/sangue , Apolipoproteínas B/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta , Carboidratos da Dieta/sangue , Gorduras na Dieta/sangue , Ácidos Graxos Monoinsaturados/sangue , Feminino , Genótipo , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
11.
BMC Med ; 16(1): 136, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30089491

RESUMO

BACKGROUND: Online dietary assessment tools can reduce administrative costs and facilitate repeated dietary assessment during follow-up in large-scale studies. However, information on bias due to measurement error of such tools is limited. We developed an online 24-h recall (myfood24) and compared its performance with a traditional interviewer-administered multiple-pass 24-h recall, assessing both against biomarkers. METHODS: Metabolically stable adults were recruited and completed the new online dietary recall, an interviewer-based multiple pass recall and a suite of reference measures. Longer-term dietary intake was estimated from up to 3 × 24-h recalls taken 2 weeks apart. Estimated intakes of protein, potassium and sodium were compared with urinary biomarker concentrations. Estimated total sugar intake was compared with a predictive biomarker and estimated energy intake compared with energy expenditure measured by accelerometry and calorimetry. Nutrient intakes were also compared to those derived from an interviewer-administered multiple-pass 24-h recall. RESULTS: Biomarker samples were received from 212 participants on at least one occasion. Both self-reported dietary assessment tools led to attenuation compared to biomarkers. The online tools resulted in attenuation factors of around 0.2-0.3 and partial correlation coefficients, reflecting ranking intakes, of approximately 0.3-0.4. This was broadly similar to the more administratively burdensome interviewer-based tool. Other nutrient estimates derived from myfood24 were around 10-20% lower than those from the interviewer-based tool, with wide limits of agreement. Intraclass correlation coefficients were approximately 0.4-0.5, indicating consistent moderate agreement. CONCLUSIONS: Our findings show that, whilst results from both measures of self-reported diet are attenuated compared to biomarker measures, the myfood24 online 24-h recall is comparable to the more time-consuming and costly interviewer-based 24-h recall across a range of measures.


Assuntos
Biomarcadores/química , Técnicas e Procedimentos Diagnósticos/estatística & dados numéricos , Dieta/métodos , Avaliação Nutricional , Adolescente , Adulto , Idoso , Educação a Distância , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Projetos de Pesquisa , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
12.
J Breath Res ; 12(4): 046006, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30015629

RESUMO

BACKGROUND: The appetite-regulating effects of non-digestible carbohydrates (NDC) have in part previously been attributed to their effects on intestinal transit rates as well as microbial production of short chain fatty acids (SCFA). Increased colonic production of the SCFA propionate has been shown to reduce energy intake and stimulate gut hormone secretion acutely in humans. OBJECTIVE: We investigated the effect of the propiogenic NDC, L-rhamnose, on gastrointestinal transit times using a combined 13CO2/H2 breath test. We hypothesised that L-rhamnose would increase plasma propionate leading to a reduction in appetite, independent of changes in gastrointestinal transit times. DESIGN: We used a dual 13C-octanoic acid/lactose 13C-ureide breath test combined with breath H2 to measure intestinal transit times following the consumption of 25 g d-1 L-rhamnose, compared with inulin and cellulose, in 10 healthy humans in a randomised cross-over design pilot study. Gastric emptying (GE) and oro-caecal transit times (OCTTs) were derived from the breath 13C data and compared with breath H2. Plasma SCFA and peptide YY (PYY) were also measured alongside subjective measures of appetite. RESULTS: L-rhamnose significantly slowed GE rates (by 19.5 min) but there was no difference in OCTT between treatments. However, breath H2 indicated fermentation of L-rhamnose before it reached the caecum. OCTT was highly correlated with breath H2 for inulin but not for L-rhamnose or cellulose. L-rhamnose consumption significantly increased plasma propionate and PYY but did not significantly reduce subjective appetite measures. CONCLUSIONS: The NDCs tested had a minimal effect on intestinal transit time. Our data suggest that L-rhamnose is partially fermented in the small intestine and that breath H2 reflects the site of gastrointestinal fermentation and is only a reliable marker of OCTT for certain NDCs (e.g. inulin). Future studies should focus on investigating the appetite-suppressing potential of L-rhamnose and verifying the findings in a larger cohort.


Assuntos
Regulação do Apetite/efeitos dos fármacos , Testes Respiratórios/métodos , Dióxido de Carbono/análise , Isótopos de Carbono/química , Ácidos Graxos Voláteis/metabolismo , Trânsito Gastrointestinal/efeitos dos fármacos , Hidrogênio/análise , Ramnose/farmacologia , Ceco/efeitos dos fármacos , Celulose/administração & dosagem , Celulose/farmacologia , Estudos Cross-Over , Ácidos Graxos Voláteis/sangue , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Trânsito Gastrointestinal/fisiologia , Humanos , Inulina/administração & dosagem , Inulina/farmacologia , Masculino , Pessoa de Meia-Idade , Peptídeo YY/sangue , Projetos Piloto , Fatores de Tempo
13.
Int J Nanomedicine ; 12: 6677-6685, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28932113

RESUMO

Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA)-encapsulated lipid-based delivery system - liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN). We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo.


Assuntos
Acetatos/administração & dosagem , Antineoplásicos/administração & dosagem , Lipídeos/química , Nanopartículas/administração & dosagem , Animais , Cátions/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Células HCT116 , Células HT29 , Histona Desacetilases/genética , Humanos , Lipossomos/química , Camundongos , Nanopartículas/química , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Clin Sci (Lond) ; 131(21): 2561-2573, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28923880

RESUMO

Dietary sugars are linked to the development of non-alcoholic fatty liver disease (NAFLD) and dyslipidaemia, but it is unknown if NAFLD itself influences the effects of sugars on plasma lipoproteins. To study this further, men with NAFLD (n = 11) and low liver fat 'controls' (n = 14) were fed two iso-energetic diets, high or low in sugars (26% or 6% total energy) for 12 weeks, in a randomised, cross-over design. Fasting plasma lipid and lipoprotein kinetics were measured after each diet by stable isotope trace-labelling.There were significant differences in the production and catabolic rates of VLDL subclasses between men with NAFLD and controls, in response to the high and low sugar diets. Men with NAFLD had higher plasma concentrations of VLDL1-triacylglycerol (TAG) after the high (P<0.02) and low sugar (P<0.0002) diets, a lower VLDL1-TAG fractional catabolic rate after the high sugar diet (P<0.01), and a higher VLDL1-TAG production rate after the low sugar diet (P<0.01), relative to controls. An effect of the high sugar diet, was to channel hepatic TAG into a higher production of VLDL1-TAG (P<0.02) in the controls, but in contrast, a higher production of VLDL2-TAG (P<0.05) in NAFLD. These dietary effects on VLDL subclass kinetics could be explained, in part, by differences in the contribution of fatty acids from intra-hepatic stores, and de novo lipogenesis. The present study provides new evidence that liver fat accumulation leads to a differential partitioning of hepatic TAG into large and small VLDL subclasses, in response to high and low intakes of sugars.


Assuntos
Carboidratos da Dieta/administração & dosagem , Gorduras/metabolismo , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Triglicerídeos/metabolismo , Adulto , Idoso , Estudos Cross-Over , Carboidratos da Dieta/farmacologia , Ensaio de Imunoadsorção Enzimática , Jejum/sangue , Humanos , Lipídeos/sangue , Lipoproteínas VLDL/sangue , Fígado/efeitos dos fármacos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Avaliação de Resultados em Cuidados de Saúde , Fatores de Tempo , Triglicerídeos/sangue
15.
J Proteome Res ; 16(3): 1280-1287, 2017 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-28145113

RESUMO

Epidemiology and clinical studies provide clear evidence of the complex links between diet and health. To understand these links, reliable dietary assessment methods are pivotal. Biomarkers have emerged as more objective measures of intake compared with traditional dietary assessment methods. However, there are only a limited number of putative biomarkers of intake successfully identified and validated. The use of biomarkers that reflect food intake to examine diet related diseases represents the next step in biomarker research. Therefore, the aim of this study was to (1) identify and confirm biomarkers associated with dietary fat intake and (2) examine the relationship between those biomarkers with health parameters. Heatmap analysis identified a panel of 22 lipid biomarkers associated with total dietary fat intake in the Metabolic Challenge (MECHE) Study. Confirmation of four of these biomarkers demonstrated responsiveness to different levels of fat intake in a separate intervention study (NutriTech study). Linear regression identified a significant relationship between the panel of dietary fat biomarkers and HOMA-IR, with three lipid biomarkers (C16, PCaaC36:2, and PCae36:4) demonstrating significant associations. Identifying such links allows us to explore the relationship between diet and health to determine whether these biomarkers can be modulated through diet to improve health outcomes.


Assuntos
Dieta , Saúde , Lipídeos/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Coortes , Gorduras na Dieta/sangue , Ingestão de Alimentos , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Nutrients ; 8(8)2016 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-27527214

RESUMO

The current UK food composition tables are limited, containing ~3300 mostly generic food and drink items. To reflect the wide range of food products available to British consumers and to potentially improve accuracy of dietary assessment, a large UK specific electronic food composition database (FCDB) has been developed. A mapping exercise has been conducted that matched micronutrient data from generic food codes to "Back of Pack" data from branded food products using a semi-automated process. After cleaning and processing, version 1.0 of the new FCDB contains 40,274 generic and branded items with associated 120 macronutrient and micronutrient data and 5669 items with portion images. Over 50% of food and drink items were individually mapped to within 10% agreement with the generic food item for energy. Several quality checking procedures were applied after mapping including; identifying foods above and below the expected range for a particular nutrient within that food group and cross-checking the mapping of items such as concentrated and raw/dried products. The new electronic FCDB has substantially increased the size of the current, publically available, UK food tables. The FCDB has been incorporated into myfood24, a new fully automated online dietary assessment tool and, a smartphone application for weight loss.


Assuntos
Bases de Dados Factuais , Análise de Alimentos , Avaliação Nutricional , Tamanho da Porção , Adulto , Carboidratos da Dieta/análise , Gorduras na Dieta/análise , Proteínas na Dieta/análise , Ingestão de Energia , Alimentos/economia , Rotulagem de Alimentos , Alimentos em Conserva/análise , Humanos , Internet , Micronutrientes/análise , Aplicativos Móveis , Valor Nutritivo , Controle de Qualidade , Terminologia como Assunto , Reino Unido
17.
Obesity (Silver Spring) ; 24(8): 1723-30, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27460713

RESUMO

OBJECTIVE: To assess appetite and gut hormone levels in patients following partial (PR) or total resection (TR) of the large bowel. METHODS: A comparative cross sectional study was carried out with healthy controls (n = 99) and patients who had undergone PR (n = 64) or TR (n = 12) of the large bowel. Participants consumed a standard (720 kcal) breakfast meal at 0830 (t = 0) h followed by lactulose (15 g) and a buffet lunch (t = 210 min). Participants rated the subjective feelings of hunger at t = -30, 0, 30, 60, 120, and 180 min. Breath hydrogen (BH) concentrations were also evaluated. In a matched subset (11 controls, 11 PR and 9 TR patients) PYY and GLP-1 concentrations were measured following breakfast. The primary outcome measure was appetite, as measured using visual analogue scales and the buffet lunch. The secondary outcome was BH concentrations following a test meal. RESULTS: PR and TR participants had lower hunger and energy intake at the buffet lunch meal compared to controls. PR subjects had higher BH concentrations compared to controls and TR subjects. BH levels correlated with circulating GLP-1 levels at specific time points. CONCLUSIONS: PR or TR of the large bowel reduced feelings of hunger and energy intake, and PR increased gastrointestinal fermentation.


Assuntos
Apetite , Ingestão de Alimentos , Hormônios Gastrointestinais/metabolismo , Fome , Intestino Delgado/metabolismo , Intestino Delgado/cirurgia , Adulto , Desjejum , Estudos Transversais , Ingestão de Energia , Feminino , Gastrectomia , Polipeptídeo Inibidor Gástrico/metabolismo , Humanos , Almoço , Masculino , Obesidade/cirurgia
18.
Am J Clin Nutr ; 104(1): 5-14, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27169834

RESUMO

BACKGROUND: Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable. OBJECTIVES: We investigated the effect of increased colonic propionate production on brain anticipatory reward responses during food picture evaluation. We hypothesized that elevated colonic propionate would reduce both reward responses and ad libitum energy intake via stimulation of anorexigenic gut hormone secretion. DESIGN: In a randomized crossover design, 20 healthy nonobese men completed a functional magnetic resonance imaging (fMRI) food picture evaluation task after consumption of control inulin or inulin-propionate ester, a unique dietary compound that selectively augments colonic propionate production. The blood oxygen level-dependent (BOLD) signal was measured in a priori brain regions involved in reward processing, including the caudate, nucleus accumbens, amygdala, anterior insula, and orbitofrontal cortex (n = 18 had analyzable fMRI data). RESULTS: Increasing colonic propionate production reduced BOLD signal during food picture evaluation in the caudate and nucleus accumbens. In the caudate, the reduction in BOLD signal was driven specifically by a lowering of the response to high-energy food. These central effects were partnered with a decrease in subjective appeal of high-energy food pictures and reduced energy intake during an ad libitum meal. These observations were not related to changes in blood peptide YY (PYY), glucagon-like peptide 1 (GLP-1), glucose, or insulin concentrations. CONCLUSION: Our results suggest that colonic propionate production may play an important role in attenuating reward-based eating behavior via striatal pathways, independent of changes in plasma PYY and GLP-1. This trial was registered at clinicaltrials.gov as NCT00750438.


Assuntos
Regulação do Apetite , Colo/metabolismo , Corpo Estriado/metabolismo , Sinais (Psicologia) , Ingestão de Energia , Propionatos/metabolismo , Recompensa , Adulto , Antecipação Psicológica , Apetite , Glicemia/metabolismo , Estudos Cross-Over , Hormônios Gastrointestinais/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Inulina/farmacologia , Masculino , Refeições , Pessoa de Meia-Idade , Vias Neurais , Peptídeo YY/sangue , Resposta de Saciedade
19.
Br J Nutr ; 116(2): 360-74, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27198187

RESUMO

Dietary mycoprotein decreases energy intake in lean individuals. The effects in overweight individuals are unclear, and the mechanisms remain to be elucidated. This study aimed to investigate the effect of mycoprotein on energy intake, appetite regulation, and the metabolic phenotype in overweight and obese volunteers. In two randomised-controlled trials, fifty-five volunteers (age: 31 (95 % CI 27, 35) years), BMI: 28·0 (95 % CI 27·3, 28·7) kg/m2) consumed a test meal containing low (44 g), medium (88 g) or high (132 g) mycoprotein or isoenergetic chicken meals. Visual analogue scales and blood samples were collected to measure appetite, glucose, insulin, peptide tyrosine-tyrosine (PYY) and glucagon-like peptide-1 (GLP-1). Ad libitum energy intake was assessed after 3 h in part A (n 36). Gastric emptying by the paracetamol method, resting energy expenditure and substrate oxidation were recorded in part B (n 14). Metabonomics was used to compare plasma and urine samples in response to the test meals. Mycoprotein reduced energy intake by 10 % (280 kJ (67 kcal)) compared with chicken at the high content (P=0·009). All mycoprotein meals reduced insulin concentrations compared with chicken (incremental AUClow (IAUClow): -8 %, IAUCmedium: -12 %, IAUChigh: -21 %, P=0·004). There was no significant difference in glucose, PYY, GLP-1, gastric emptying rate and energy expenditure. Following chicken intake, paracetamol-glucuronide was positively associated with fullness. After mycoprotein, creatinine and the deamination product of isoleucine, α-keto-ß-methyl-N-valerate, were inversely related to fullness, whereas the ketone body, ß-hydroxybutyrate, was positively associated. In conclusion, mycoprotein reduces energy intake and insulin release in overweight volunteers. The mechanism does not involve changes in PYY and GLP-1. The metabonomics analysis may bring new understanding to the appetite regulatory properties of food.


Assuntos
Apetite/efeitos dos fármacos , Proteínas na Dieta/farmacologia , Ingestão de Energia/efeitos dos fármacos , Proteínas Fúngicas/farmacologia , Hormônios Gastrointestinais/sangue , Insulina/sangue , Obesidade , Adulto , Animais , Apetite/fisiologia , Regulação do Apetite/fisiologia , Proteínas na Dieta/uso terapêutico , Dipeptídeos/sangue , Ingestão de Alimentos/fisiologia , Feminino , Proteínas Fúngicas/uso terapêutico , Fusarium/química , Esvaziamento Gástrico/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/dietoterapia , Obesidade/fisiopatologia , Peptídeo YY/sangue , Período Pós-Prandial , Aves Domésticas , Saciação/efeitos dos fármacos , Adulto Jovem
20.
Ann Nutr Metab ; 68(1): 26-34, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26571012

RESUMO

BACKGROUND: Fermentable carbohydrates (FCHO) have been shown to improve insulin sensitivity in normoglycaemic and insulin-resistant subjects. However, there are no data on subjects with prediabetes. We aimed to investigate the effect of the FCHO inulin, on glucose homeostasis in subjects with prediabetes. METHODS: In a double-blind and placebo-controlled crossover study, 40 volunteers with prediabetes were randomly allocated to take 30 g/day of inulin or cellulose for 2 weeks in a crossover trial, following a 4-week dose-escalation run-in. Fasting insulin and glucose were measured for all subjects. Fifteen of the 40 subjects also underwent a meal tolerance test to assess insulin sensitivity, free fatty acids and glucagon-like peptide-1 concentrations. A subanalysis was carried out to examine any differences between the prediabetes subtypes. RESULTS: Inulin was associated with a significant increase in (0-30 min)incremental AUC (iAUC) for insulin (treatment: p < 0.04) and (0-60 min)iAUC for insulin (treatment: p < 0.04) compared to control. There was a significant reduction in insulin resistance measured by the homeostatic model assessment in the isolated-impaired fasting glucose (p < 0.05) but not in the isolated-impaired glucose tolerance groups (p = 0.59). CONCLUSION: The FCHO, inulin, may have unique metabolic effects that are of particular benefit to people at risk of diabetes, which warrant further investigation.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Homeostase , Inulina/administração & dosagem , Estado Pré-Diabético/tratamento farmacológico , Idoso , Índice de Massa Corporal , Estudos Cross-Over , Método Duplo-Cego , Ácidos Graxos não Esterificados/sangue , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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